Brand Names: U.S.

Adderall

Adderall XR

Pharmacologic Category

Central Nervous System Stimulant

Pharmacology

Amphetamines are noncatecholamine, sympathomimetic amines that promote release of catecholamines (primarily dopamine and norepinephrine) from their storage sites in the presynaptic nerve terminals. A less significant mechanism may include their ability to block the reuptake of catecholamines by competitive inhibition.

Absorption

Well-absorbed. Adderall XR: Food does not affect absorption but prolongs Tmax by 2 to 3 hours.

Use: Labeled Indications

Attention-deficit/hyperactivity disorder (ADHD); narcolepsy

Contraindications

Hypersensitivity or idiosyncrasy to the sympathomimetic amines; advanced arteriosclerosis; symptomatic cardiovascular disease; moderate-to-severe hypertension; hyperthyroidism; hypersensitivity or idiosyncrasy to the sympathomimetic amines; glaucoma; agitated states; patients with a history of drug abuse; during or within 14 days following MAO inhibitor (hypertensive crisis)

Dosing: Adult

Note: Use lowest effective individualized dose; administer first dose as soon as awake.

Adderall XR: Initial: 20 mg once daily in the morning; higher doses (up to 60 mg once daily) have been evaluated; however, there is not adequate evidence that higher doses afforded additional benefit. The Canadian labeling recommends a maximum dose of 30 mg/day.

Conversion from immediate release to extended release formulation: Patients may be switched from the immediate release formulation to the extended release formulation using the same total daily dose once daily.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Use lowest effective individualized dose; administer first dose as soon as awake.

ADHD: Oral:

Children: <3 years: Not recommended.

Children: 3 to 5 years (Adderall): Initial 2.5 mg once daily given every morning; increase daily dose in 2.5 mg increments at weekly intervals until optimal response is obtained; maximum dose: 40 mg daily given in 1 to 3 divided doses per day. Use intervals of 4 to 6 hours between additional doses.

Conversion from immediate release to extended release formulation: Patients may be switched from the immediate release formulation to the extended release formulation using the same total daily dose once daily.

Adderall XR: 10 mg once daily in the morning; maybe increased to 20 mg daily after 1 week if symptoms are not controlled; higher doses (up to 60 mg)/day have been evaluated; however, there is not adequate evidence that higher doses afforded additional benefit. The Canadian labeling recommends a maximum dose of 30 mg/day.

Conversion from immediate release to extended release formulation: Patients may be switched from the immediate release formulation to the extended release formulation using the same total daily dose once daily.

Hemodialysis: There are no specific dosage adjustments provided in the manufacturer’s labeling; however, the manufacturer recommends considering further dosage reductions (compared to that recommended for severe impairment). Dextroamphetamine is not dialyzable.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Extemporaneously Prepared

A 1 mg/mL oral suspension may be made with tablets. Crush ten 10 mg tablets in a mortar and reduce to a fine powder. Add small portions of Ora-Sweet and mix to a uniform paste; mix while adding the vehicle in equal proportions to almost 100 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add sufficient quantity of vehicle to make 100 mL. Label "shake well". Stable 30 days at room temperature.

Administration

May be administered without regard to meals. If possible, therapy should occasionally be interrupted to determine if continued therapy is needed.

Adderall: To avoid insomnia, late evening doses should be avoided.

Adderall XR: Administer first dose as soon as awake; should be given by noon. Capsule may be swallowed whole or it may be opened and the contents sprinkled on applesauce. Applesauce should be consumed immediately without chewing. Do not divide the contents of the capsule.

Cocaine: May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Lithium: May diminish the stimulatory effect of Amphetamines. Monitor therapy

MAO Inhibitors: May enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Tedizolid. Avoid combination

Methenamine: May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Monitor therapy

Multivitamins/Fluoride (with ADE): May decrease the serum concentration of Amphetamines. More specifically, the ascorbic acid (vitamin C) in many multivitamins may decrease amphetamine concentrations. Monitor therapy

Proton Pump Inhibitors: May increase the absorption of Dextroamphetamine. Specifically, the dextroamphetamine absorption rate from mixed amphetamine salt extended release (XR) capsules may be increased in the first hours after dosing. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Tricyclic Antidepressants: May enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Monitor therapy

ALERT: U.S. Boxed Warning

Abuse potential:

Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence and must be avoided. Particular attention should be paid to the possibility of persons obtaining amphetamines for nontherapeutic use or distribution to others, and the drugs should be prescribed or dispensed sparingly.

Cardiovascular events:

Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular events: [U.S. Boxed Warning]: Use has been associated with serious cardiovascular events including sudden death in patients with preexisting structural cardiac abnormalities or other serious heart problems (sudden death in children and adolescents; sudden death, stroke and MI in adults). These products should be avoided in the patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that could increase the risk of sudden death that these conditions alone carry. Patients should be carefully evaluated for cardiac disease prior to initiation of therapy. Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during treatment should undergo a prompt cardiac evaluation.

• Peripheral vasculopathy: Stimulants are associated with peripheral vasculopathy, including Raynaud’s phenomenon; signs/symptoms are usually mild and intermittent, and generally improve with dose reduction or discontinuation. Digital ulceration and/or soft tissue breakdown have been observed rarely; monitor for digital changes during therapy and seek further evaluation (eg, rheumatology) if necessary.

• Visual disturbance: Difficulty in accommodation and blurred vision has been reported with the use of stimulants.

Disease-related concerns:

• Abuse potential: [U.S. Boxed Warning]: Potential for drug dependency exists; prolonged use may lead to drug dependency. Use is contraindicated in patients with history of drug abuse. Prescriptions should be written for the smallest quantity consistent with good patient care to minimize possibility of overdose.

• Hypertension: Use with caution in patients with hypertension and other cardiovascular conditions that might be exacerbated by increases in blood pressure or heart rate. Use is contraindicated in patients with moderate to severe hypertension.

• Psychiatric disorders: Use with caution in patients with preexisting psychosis or bipolar disorder (may induce mixed/manic episode). May exacerbate symptoms of behavior and thought disorder in psychotic patients; new onset psychosis or mania may occur with stimulant use; observe for symptoms of aggression and/or hostility. Screen patients with comorbid depressive symptoms prior to initiating treatment to determine if they are at risk for bipolar disorder.

• Seizure disorder: Limited information exists regarding amphetamine use in seizure disorder (Cortese, 2013). The manufacturer recommends use with caution in patients with a history of seizure disorder; may lower seizure threshold leading to new onset or breakthrough seizure activity.

• Tourette syndrome: Use with caution in patients with Tourette syndrome; stimulants may unmask tics.

Special populations:

• Pediatric: Appetite suppression may occur; monitor weight during therapy, particularly in children. Use of stimulants has been associated with suppression of growth; monitor growth rate during treatment. Not recommended for children younger than 3 years.

Other warnings/precautions:

• Discontinuation of therapy: Abrupt discontinuation following high doses or for prolonged periods may result in symptoms for withdrawal.

Monitoring Parameters

When used for the treatment of ADHD, perform a targeted cardiac history (eg, patient history of previously detected cardiac disease, palpitations, syncope, or seizures; family history of sudden death in children or young adults; hypertrophic cardiomyopathy; long QT syndrome) and physician examination including cardiac examination. Monitor heart rate and blood pressure (baseline; follow-up within 1 to 3 months and routinely at 6 to 12 month intervals thereafter unless clinically indicated with dose titration and weaning of therapy) Consider obtaining ECG prior to initiation (Perrin, 2008; Vetter, 2008).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse effects have been observed in animal reproduction studies. The majority of human data is based on illicit amphetamine/methamphetamine exposure and not from therapeutic maternal use (Golub, 2005). Use of amphetamines during pregnancy may lead to an increased risk of premature birth and low birth weight; newborns may experience symptoms of withdrawal. Behavioral problems may also occur later in childhood (LaGasse, 2012).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.